Laboni Mondal

Colloidal gold-loaded, biodegradable, polymer-based stavudine nanoparticle uptake by macrophages: an in vitro study.

Video abstract Video

Pulmonary Delivery of Voriconazole Loaded Nanoparticles Providing a Prolonged Drug Level in Lungs: A Promise for Treating Fungal Infection.

Current therapies are insufficient to prevent recurrent fungal infection especially in the lower part of the lung. A careful and systematic understanding of the properties of nanoparticles plays a significant role in the design, development, optimization, and in vivo performances of the nanoparticles. In the present study, PLGA nanoparticles containing the antifungal drug voriconazole was prepared and two best formulations were selected for further characterization and in vivo studies. The nanoparticles and the free drug were radiolabeled with technetium-99m with 90% labeling efficiency, and the radiolabeled particles were administered to investigate the effect on their blood clearance, biodistribution, and in vivo gamma imaging. In vivo deposition of the drug in the lobes of the lung was studied by LC-MS/MS study. The particles were found to be spherical and had an average hydrodynamic diameter of 300 nm with a smooth surface. The radiolabeled particles and the free drug were found to accumulate in various major organs. Drug accumulation was more pronounced in the lung in the case of administration of the nanoparticles than that of the free drug. The free drug was found to be excreted more rapidly than the nanoparticle containing drug following the inhalation route as assessed by gamma scintigraphy study. Thus, the study reveals that pulmonary administration of nanoparticles containing voriconazole could be a better therapeutic choice even as compared to the iv route of administration of the free drug and/or the drug loaded nanoparticles.

Obesity and Insulin Resistance: An Abridged Molecular Correlation

A relationship between obesity and type 2 diabetes is now generally well accepted. This relationship represents several major health hazards including morbid obesity and cardiovascular complications worldwide. Diabetes mellitus is a complex metabolic disorder characterized by impaired insulin release and insulin resistance. Lipids play an important physiological role in skeletal muscle, heart, liver and pancreas. Deregulation of fatty acid metabolism is the main culprit for developing insulin resistance and type 2 diabetes. A predominant predisposing factor to developing obesity, insulin resistance and type 2 diabetes is the permanent elevation of free fatty acids in plasma followed by impaired utilization of lipids by muscle. Diabetes-induced inflammation and oxidative stress have also vital role for development of insulin resistance in diabetic patients. The present review is intended to describe the correlation between lipids, obesity and insulin resistance based on current literature, in order to elucidate involved molecular mechanisms in depth.

Potentials and Challenges of Active Targeting at the Tumor Cells by Engineered Polymeric Nanoparticles

Tumor targeted therapy has brought a new hope to the cancer patients. With the recent advances in nanotechnology and growing knowledge on unique cancer biomarkers, it is now possible to manipulate the surface architecture of polymeric nanoscale delivery systems with targeting moieties, such as antibodies, antibody fragments, specific molecules, small peptides, RNA aptamers etc. to target specific receptors and antigens present exclusively or overexpressed on the tumor cell surface or on the tumor endothelial cell surface. These modified polymeric nanoparticles deliver the loaded chemotherapeutics preferentially to the tumor tissue and not to the healthy tissue. This ensures highly targeted treatment without severe side effects which are normally experienced by the cancer patients in case of conventional chemotherapy. Such specifically constructed polymeric nanocarriers with improved tumor targeting profile are now regarded as engineered polymeric nanoparticles, which have become one of the prime areas of drug delivery research in recent times. This review describes specific approaches used in recent years to construct engineered polymeric nanoparticles, their emerging potential for cancer therapy and recent advances in tumor targeting. An equal attention has been devoted to the fundamental problems encountered in practical fields which limit their clinical use and industrial production.

Size Dependent Variations of Phospholipid Based Vesicular Drug Carriers in Systemic Drug Activity

Lipid based vesicular drug delivery system, one of the emerging technologies designed for addressing the delivery challenges of conventional drug delivery methods, has widespread applications in chemotherapeutics, immunotherapeutics, recombinant DNA technology, membrane biology and also as a diagnostic tool in different biological field. The enclosed phospholipid bilayer spherical structure, typically known as liposome, is a versatile vesicular delivery system to carry hydrophilic/hydrophobic drug generally efficiently to the site of action leading to reduced non-specific toxicity and improved bioavailability of the therapeutic moiety. Efficacy of drug encapsulated in liposome depends mainly on the circulation amount of liposome and its residence time, in vivo drug release, drug accumulation in the target site and uptake of the formulation in the reticuloendothelial system. Liposomal formulation factors that dictate those actions are liposomal size (hydrodynamic diameter), surface charge, lipid composition and steric stabilization. Variation in liposomal size shows around 100 fold alterations in pharmacokinetic parameters and systemic activity while the other factors such as surface charge, lipid composition and steric stabilization bring only about 10 fold changes in those properties. The findings indicate the critical role of vesicular size in liposomal efficacy. In the present review the effect of size-variation of liposome on systemic activity of drug as well as its pharmacokinetic profile will be discussed to understand the rational designing of liposomal preparation to maximize therapeutic activity of a drug at desired magnitude and to provide a wide range of product applications such as immunological vaccines, chemotherapy, antimicrobial therapy etc.

Potentials of polymeric nanoparticle as drug carrier for cancer therapy: with a special reference to pharmacokinetic parameters.

Nanomaterials have made a significant impact on cancer therapeutics and an emergence of polymeric nanoparticle provides a unique platform for delivery of drug molecules of diverse nature. Nanoparticles can be targeted at the tumor cells due to enhanced permeability and retention effect. Moreover, nanoparticles can be grafted by various ligands on their surface to target the specific receptors overexpressed by cancer cells or angiogenic endothelial cells. These approaches ultimately result in longer circulation half-lives, improved drug pharmacokinetics, reduced side effects of therapeutically active substances and overcoming cancer chemo-resistance thereby enhancing the therapeutic efficacy of the treatment. This review article summarizes the recent efforts in cancer nanochemotherapeutics using polymeric nanoparticles with a special reference to their pharmacokinetic and biodistribution profiles, their role in reversing multidrug resistance in cancer and strategies of tumor targeting with them, along with the challenges in the field.

Multifunctional drug nanocarriers facilitate more specific entry of therapeutic payload into tumors and control multiple drug resistance in cancer

Abstract Cancer in its various forms is considered as one of the world’s most devastating diseases. The triumph over cancer depends on the ability of therapeutics to reach the particular intracellular and intercellular targets, while lessening their accumulation at nonspecific sites. The advancement in nanotechnology and biotechnology has contributed immensely to the development of biocompatible nanocarriers adapted to specific needs and they have the ability to deliver therapeutic payloads specifically to the target tissue(s). The microenvironment of tumors possesses several unique features, thus the knowledge and understandings of tumor microenvironment are crucial for the development of nanocarriers targeted towards several specific types of tumors. Nanocarriers also possess the potential of delivering multiple drugs directed against different molecular targets, resulting in suppression of multidrug-resistant phenotypes as well as a decrease in multidrug-resistant based drug efflux. Surface amendment with various polymers, such as polyethylene glycol, improves circulation time by minimizing nonspecific uptake while inclusion of active targeting ligands allow for more precise tumor targeting. This chapter focuses on the modalities for overcoming different physiological barriers to tumor targeting using different types of multifunctional target-specific nanocarriers to facilitate more specific entry of drugs into the tumor for better therapeutic outcome, along with future directives to improve the frequency of translation of nanomedicine from laboratories to clinic.

Apigenin loaded nanoparticle delayed development of hepatocellular carcinoma in rats

Hepatocellular carcinoma (HCC) is one of the major causes of cancer related death globally. Apigenin, a dietary flavonoid, possesses anti-tumor activity against HCC cells in-vitro. Development, physicochemical characterization of apigenin loaded nanoparticles (ApNp), biodistribution pattern and pharmacokinetic parameters of apigenin upon intravenous administration of ApNp, and effect of ApNp treatment in rats with HCC were investigated. Apigenin loaded nanoparticles had a sustained drug release pattern and successfully reached the hepatic cancer cells in-vitro as well as in liver of carcinogenic animals. ApNp predominantly delayed the progress of HCC in chemical induced hepatocarcinogenesis in rats. Quantification of apigenin by liquid chromatography-mass spectroscopy (LC-MS/MS) showed that apigenin availability significantly increased in blood and liver upon ApNp treatment. Apigenin loaded nanoparticle delivery substantially controlled the severity of hepatocellular carcinoma and could be a future hope for lingering the survival in hepatic cancer patients.

Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood–brain barrier into brain

Abstract Delivering highly water soluble drugs across blood–brain barrier (BBB) is a crucial challenge for the formulation scientists. A successful therapeutic intervention by developing a suitable drug delivery system may revolutionize treatment across BBB. Efforts were given here to unravel the capability of a newly developed fatty acid combination (stearic acid:oleic acid:palmitic acid = 8.08:4.13:1) (ML) as fundamental component of nanocarrier to deliver highly water soluble zidovudine (AZT) as a model drug into brain across BBB. A comparison was made with an experimentally developed standard phospholipid-based nanocarrier containing AZT. Both the formulations had nanosize spherical unilamellar vesicular structure with highly negative zeta potential along with sustained drug release profiles. Gamma scintigraphic images showed both the radiolabeled formulations successfully crossed BBB, but longer retention in brain was observed for ML-based formulation (MGF) as compared to soya lecithin (SL)-based drug carrier (SYF). Plasma and brain pharmacokinetic data showed less clearance, prolonged residence time, more bioavailability and sustained release of AZT from MGF in rats compared to those data of the rats treated with SYF/AZT suspension. Thus, ML may be utilized to successfully develop drug nanocarrier to deliver drug into brain across BBB, in a sustained manner for a prolong period of time and may provide an effective therapeutic strategy for many diseases of brain. Further, many anti-HIV drugs cannot cross BBB sufficiently. Hence, the developed formulation may be a suitable option to carry those drugs into brain for better therapeutic management of HIV.

Pulmonary Administration of Biodegradable Drug Nanocarriers for More Efficacious Treatment of Fungal Infections in Lungs: Insights Based on Recent Findings

Lung fungal infection is a critical health problem, particularly in immunocompromised patients suffering from lung cancer, cystic fibrosis, HIV infection, etc. Due to rapid blood turnover in lungs, conventional drug delivery systems do not offer persistent blood level of drug in the lungs, causing inadequate drug bioavailability locally. Hence, a large amount of dose is generally required for a prolonged period, causing toxicity. The patients, therefore, cannot tolerate the treatment, and recurrence of fungal infection by the fungal spores may occur even after the conventional treatment requiring long-term medication. The pulmonary administration of drug nanocarriers thus may prove to be an underrated approach since this is a noninvasive method for local as well as systemic drug delivery, with various additional advantages, such as a large surface area with quick absorption, over other routes of administration, and local delivery of the medication for a prolonged time period. Devices, such as nebulizers, metered dose inhalers, and dry powder inhalers are used for delivering the drugs through the pulmonary route. Thus, the aim of this chapter is to summarize the recent findings related to the delivery of biodegradable nanocarriers for treating fungal lung infection through the pulmonary route.